Good news today at the cardiologist’s office. With six months passing since the placement of my last set of stents, I admit to possessing a certain amount of pessimism concerning my prospects prior to the test. Post test, I was disappointed. Clocking in at 10:40 and comparing that to my record of 15:30 left me a little shell-shocked generic cialis price. Convinced another intervention waited just around the corner, my mood sour with anticipation, one can imagine my surprise at the positive results.

It is possible to explain the angina I feel during heavy exercise, and the poor time performance on the treadmill to my very low testosterone levels (see previous post). Currently, my total-T is around 180 ng/dL (normal is above 250 ng/dL), with my bioavailable testosterone coming in around the low end of normal. This is the first test since stopping testosterone replacement therapy and I have yet to begin the HPTA (hypothalmic, pituitary, testicular axis) normalization protocol.

This is a topic dear to my heart. I need to add to my story the fact that I am hypogonadal and my hypogonadism (low testosterone) is addressed with Testim, a gel I rub on my shoulders in the morning. When I stopped using the Testim, my testosterone is slowly recovering.

However, in an effort to “jump start” my testosterone production my primary doctor, in concert with an expert in Houston, is prepared to start me on HCG (human chrorionic hormone), Nolvadex, and Clomid. Not to get too technical, but HCG acts like luteinizing hormone (LH) which stimulates the testicles to generate testosterone. Nolvadex and Clomid are anti-estogens, and Nolvadex’s extra benefit of making the pituitary gland more sensitive to GnRH is an added bonus. GnRH (Gonadotropin Releasing Hormone) is a hormone release by the hypothalamus to the pituitary gland, resulting in the gland releasing LH to the testicles, which in turn create more testosterone.

If all goes well, normalization for me should occur within 1-3 months, instead of 12 months or more. However, in two weeks I will know whether my testicles are capable of producing the needed testosterone from their response to the HCG injections. If normalization does not occur, I will be back on the Testim.

This brings me to the main point of this post. Is heart disease caused by low testosterone, or visa versa? Here is an excellent interview with Hugh Jones, MD on the subject. This is an area just screaming for more study. Also, to my knowledge no study of the effects of testosterone on endothelial coverage of a stent has been done. Some snippets from the article:

For the sake of heart disease research, 809 members of the Old Order Amish community agreed to go to a clinic in Lancaster, Pa., near their homes, and drink a rich milkshake that was made mostly of heavy cream. Over the next six hours, a group of investigators took samples of their blood, determining how much fat was churning through their bloodstreams.

Most of the study participants responded as expected — their levels of triglycerides, a common form of fat in the blood, rose steadily for three to four hours and then declined. But about 5 percent had an extraordinary reaction: their triglyceride levels started out low and hardly budged.

It turns out, the researchers report in the Friday issue of the journal Science, that those individuals who barely responded have a mutation that disables one of their two copies of a gene called apoC-III. The gene codes for a protein, APOC3, that normally slows the breakdown of triglycerides.

With the mutated gene, people break down triglycerides unusually quickly. And, the investigators find, they also have low levels of LDL cholesterol, which at high levels increases heart disease risk. They have high levels of HDL cholesterol, which is associated with a decreased risk of heart disease. And they appear to have arteries relatively clear of plaque.

The article goes on to say that clinical applications are “years away”.

Surgeons at The Methodist Hospital in Houston were the first in the nation Thursday to inject highly-concentrated stem cells directly into a patient’s heart, providing an intense, direct hit on damaged heart tissue.

In an investigational study of new heart failure treatments, this promising new technique may be more effective in regenerating healthy heart tissue than current methods that use a catheter to put standard stem cells through the bloodstream into the heart.

The 58-year-old veteran and businessman is resting comfortably and is expected to be discharged this weekend.

“Some patients have such severe heart failure that their only current option is a heart transplant,” said Dr. Brian Bruckner, cardiac surgeon at the Methodist DeBakey Heart & Vascular Center in Houston. “We hope that stem cells will stimulate angiogenesis, the growth of new blood vessels, restore mechanical function in diseased heart tissue, and return patients to a much better quality of life without a transplant.”

In a novel process, the patient’s strongest and most robust stem and progenitor cells, derived from the patient’s own bone marrow, are amplified up to 1,000 times before they’re injected back into the patient’s heart. In the procedure, Dr. Bruckner made a small incision in the left side of the patient’s chest and administered approximately 25 injections of concentrated stem cells into the patient’s heart. All patients in the trial will be followed for 12 months after the injections.

There are currently 5.5 million people in the U.S. suffering from chronic heart failure. A subset of these patients has dilated cardiomyopathy (DCM), a chronic heart disease in which the patient’s heart can not pump effectively enough to deliver blood and oxygen to the vital organs in the body. Patients with DCM typically experience severe limitations to physical activity and shortness of breath.

“Without a new approach to treatment of these patients, they will continue to decline and less than 40 percent will survive five years,” said Bruckner, principal investigator for the trial. “We hope this trial will provide a completely new and viable treatment for them.”

Dr. Michael Reardon, chief of cardiac surgery at Methodist, and Dr. Matthias Loebe, transplant surgeon at Methodist, are co-investigators on the trial. Dr. Kevin Lisman is the patient’s referring cardiologist.

The IMPACT-DCM trial is in phase-II and is seeking to enroll 20 patients with ischemic dilated cardiomyopathy and 20 patients non-ischemic DCM patients at five clinical sites in the U.S.

For more information about the Methodist DeBakey Heart & Vascular Center, see here.

Promising news for patients with damaged heart muscles. Here is a Five Question Interview with Nenad Bursac from the Duke University Biomedical Engineering Department. Of particular note:

Patient’s own heart muscle cells will generally not divide in a sufficient number to replace the damaged part of the muscle. And if we took a larger part of the patient’s own heart muscle we would make more damage in another area, and things would only become worse. Therefore, we need an external and abundant source of cells for heart muscle repair, and a lot of research effort is ongoing to identify what that source could be. Ideally, stem cells have the potential to be this cell source for the repair of heart damage as they can be proliferated in a dish to large quantities and then potentially steered towards becoming heart cells.

But this amazing organ wasn’t part of someone’s original equipment. Instead scientists grew it in a lab. And they believe it might one day lead to new ways of treating everything from cardiac disease to transplants.

If this sounds almost inhuman, it is. The ticker actually started as the heart of a dead rat, and was taken by researchers at the University of Minnesota and “washed” of its original cells. That left a shell of the organ which the scientists then injected with new cells culled from newborn rodents. Their excitement was unbounded when the organ started beating on its own.

Those behind the project admit it has a Frankenstein-like element to it, but it also holds so much promise that’s its more boon than bane. “We really have the audacity to claim to build a functional organ from scratch so to speak,” outlines Dr. Doris Taylor. “We’re willing to admit that it’s a crazy idea.”

But what it portends is anything but crazy. The researchers admit a rat heart will never be compatible with humans – but a pig heart might be. As distasteful as that might sound, the chance that it could save the lives of thousands of patients waiting for transplants that are in too short a supply makes it worth exploring.

“Three thousand people a year don’t have other options,” Taylor explains. “We want to make a difference.”

She envisions a system where a pig heart could be “washed”, injected with stem cells from a potential recipient and literally grown from scratch, before being inserted back into the patient. Rejection would be unlikely, since the body would recognize it as its own.

NEW ORLEANS, November 9, 2008 – Celladon Corporation announced today results from the first nine patients treated with MYDICAR®, a genetically-targeted enzyme replacement therapy for advanced heart failure, showing the product was safe and demonstrating improvement across a number of key parameters. Phase 1 data from the “Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID Trial), a First-in-Human Phase 1/2 Clinical Trial” were presented at the American Heart Association Scientific Sessions 2008.

This first phase of the multi-center trial was designed to investigate safety and biological effects of restoring SERCA2a enzyme activity in heart muscle cells. The enzyme levels are decreased in late stages of heart failure, and extensive research shows loss of SERCA2a levels represents a common pathway resulting in a defect in the ability of the heart to contract properly. Replacing the enzyme may restore function and reverse heart failure.

Totally endoscopic coronary artery bypass (TECAB) is the least invasive coronary artery bypass grafting operation. The bypass graft is placed through tiny holes without any opening of the chest. In comparison to coronary artery bypass grafting procedures, which are carried out through very small openings in the chest — mini-thoracotomies — (MIDCAB, SVST), the operation is performed only through these small portholes. As a result, the surgical trauma and scarring for the patient are very minimal.

The surgeon uses a surgical robot (da Vinci system) for the procedure, which enables the surgeon to perform complex surgical maneuvers inside the chest. The surgeon inserts a video camera, which is mounted on the operation robot, into the chest and uses two or three additional instruments on the robotic arms….

…The bypass vessels are prepared inside the chest and no cutting of the leg or arms is necessary. A very small incision is made in the groin for connection of the heart-lung machine. A sophisticated special heart-lung machine system is used for these operations. This system serves as a safety net for the patient and takes over the blood circulation while the heart is stopped for the bypass graft connection. The surgeon is working on vessels that are approximately 2 to 3 millimeters in diameter. A stopped heart and the robotic system ensure very accurate suturing of tiny bypass grafts.

After the bypass grafts have been placed and the heart-lung machine is removed, the surgeon and his team check the quality of the grafts by an angiographic exam, which is done while the patient is still under general anesthesia.

A video of Dr. Johannes Bonatti performing the surgery can be found here.